莫西沙星在肺炎大鼠血液及肺组织的药代动力学研究

Study on lung pharmacokinetics of moxifloxacin in pneumonia rats

目的:观察莫西沙星灌胃给药在肺炎大鼠血液及肺组织中的药代动力学特点。方法:建立肺炎链球菌肺炎大鼠模型,莫西沙星按照42 mg·kg^(-1)灌胃给药,采用微透析技术对肺炎大鼠的血液及肺组织同步取样,应用高效液相色谱法测定莫西沙星游离药物浓度,计算药代动力学参数。结果:血液中游离药物浓度T_(max)为(1.00±0.00)h,C_(max)为(4.83±0.05)mg·L^(-1),肺组织内T_(max)为(0.95±0.10)h,C_(max)为(4.84±0.02)mg·L^(-1)。之后两者同步下降,莫西沙星在肺组织内的穿透率为(1.256±0.321)。消除半衰期(t_(1/2))在血液内为(2.16±0.12)h,肺组织内为(3.27±0.48)h(P<0.05)。血液及肺组织的AUC_((0-inf))分别为(16.94±1.52)mg·h^(-1)·L^(-1)和(18.57±1.17)mg·h^(-1)·L^(-1)(P<0.05)。分布系数(AUC_肺/AUC_(血液))为(1.216±0.041)。结论:在该剂量条件下,莫西沙星灌胃给药后,在肺炎大鼠肺组织的穿透率高,血液及肺组织内的游离药物浓度较高,远超过了最低抑菌浓度和防耐药突变浓度,可以有效清除肺炎链球菌,获得较好疗效。

Objective：To observe the pharmacokinetic characteristics of gavage moxifl oxacin in blood and lung tissues of pneumonia rats.Methods：Streptococcus pneumoniae rats were established.The rats were gavaged moxifl oxacin at the dose of42 mg·kg-1,the blood and lung tissues of pneumonia rats were sampled by microdialysis methods.The free drug concentration of moxifl oxacin was determined by HPLC method,and the related pharmacokinetic parameters were calculated.Results：In the blood,the T-max of the free drug concentration was（1.00±0.00）h,Cmax was（4.83±0.05）mg·L1.In lung tissues,Tmax was（0.95±0.10）h,Cmax was（4.84±0.02）mg·L-1.Then,both fell synchronously,the pulmonary penetration rate of moxifl oxacin was（1.256±0.321）.The elimination half-life（t1/2）was（2.16±0.12）h in the blood and（3.27±0.48）h in the lung tissues（P〈0.05）.The AUC（0-inf）of blood and lung tissues was（16.94±1.52）mg·h-1·L-1 and（18.57±1.17）mg·h-1·L-1,respectively（P〈0.05）.The distribution coeffi cient（AUClung/AUCblood）was（1.216±0.041）.Conclusion：In this dose,the penetration rate of gavage moxifl oxacin in lung tissue of pneumonia rats was higher,the concentration of free drugs in blood and lung tissue was higher than MIC and mutant prevention concentration.Moxifl oxacin can effectively eliminate Streptococcus pneumoniae,and get better effi cacy.